# Clinical Neuroimmunology of Vaccines in Brain Tumors

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $400,733

## Abstract

In brain tumors like glioblastoma (GBM), failures to develop an effective vaccine and achieve immune
checkpoint inhibition have been attributed to the extraordinary antigenic intratumoral heterogeneity of this
disease. To overcome this, successful immunotherapy for GBM will require antitumor T cells with increased
magnitude and functionality (potency) and T cells targeting multiple antigens simultaneously (diversity). We have
identified 3 strategies to accomplish these goals. First, we will confirm that conjoining neoantigen major
histocompatibility complex class I (MHCI) epitope peptides with the universal tetanus P30 class II epitope
markedly increases the potency of T cell responses and unveils T cells responses against MHC I antigens that
are otherwise non-immunogenic, resulting in de novo immune responses capable of inducing antitumor efficacy.
Second, we will administer P30 in the tumor microenvironment to stimulate P30-specific CD4+ T cell help. Help
provided to CD8+ T cells at the tumor during the effector stage has been shown to improve the magnitude and
persistence of CD8+ tumor infiltrating lymphocytes. Third, we will engage a novel, clinically-available checkpoint
agonist CD27) and program cell death protein 1 (PD-1) blockade. Stimulating CD27 on antigen-engaged, CD4+
and CD8+ T cells increases the immunogenicity and memory of low-affinity CD8 epitopes, and improves the
survival, effector function, and migratory capacity of activated T cells. However, as CD27 stimulation can cause
expression of inhibitory PD-1 on T cells, we will also explore PD-1 blockade as a way of limiting this escape
mechanism and further enhancing efficacy. We propose that multi-antigen P30-conjoined class I neoantigen
vaccination with the novel checkpoint agonist CD27 and PD-1 blockade will increase the potency and diversity
of neoantigen-specific CD8+ T cell responses, resulting in improved antitumor efficacy. Thus, despite a low
mutational burden in GBM, our strategy should enable potent neoantigen-specific T cell responses against a
breadth of targets to engender efficacy against heterogeneous tumor. Our Specific Aims are:
1. To determine if multi-antigen, conjoined neoantigen vaccination improves survival in mice with heterogeneous
 intracerebral glioma;
2. To determine if the addition of class II antigen at the tumor site improves efficacy in these tumors;
3. To determine if CD27, alone or in combination with PD-1 blockade, increases the potency and diversity of
 tumor-specific T cell responses and antitumor efficacy against heterogeneous tumors.

## Key facts

- **NIH application ID:** 10348190
- **Project number:** 5R01NS116888-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Qijing Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,733
- **Award type:** 5
- **Project period:** 2021-02-15 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348190

## Citation

> US National Institutes of Health, RePORTER application 10348190, Clinical Neuroimmunology of Vaccines in Brain Tumors (5R01NS116888-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10348190. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*